Quaternary ammonium (QA) compounds, in which one ethyl group of the tetraethyl-ammonium ion was replaced by a long chain alkane from four to sixteen carbons, were tested for block of the compound action potential (CAP) of frog sciatic nerve in vitro, and their duration of sensory analgesia of the rat trigeminal nerve in vivo. There was a strong relationship between chain length, blocking potency, and frequency dependence of inhibition in vitro, and in vivo a duration of action from two hours to two weeks dependent on chain length. The sensory-motor dissociation and ultralong action of these compounds suggests that they will be a useful new class of local anesthetics. Future studies will center on the site of action, metabolism, and toxicity of the QA compounds. Another branch of investigation involves increasing the duration of action of conventional local anesthetics. The addition of tetrodotoxin or saxitoxin to a local anesthetic prolongs the duration several fold. Other compounds will also be tested for their synergism with local anesthetics including: QA compounds, albumin, guanidinium compounds, and alcohols.